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Review Article
A Systematic Review of the Efficacy of Centella asiatica
for Improvement of the Signs and Symptoms of Chronic
Venous Insufficiency
Nyuk Jet Chong and Zoriah Aziz
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
Correspondence should be addressed to Zoriah Aziz; zoriah@um.edu.my
Received July ; Accepted December
Academic Editor: Yoshiyuki Kimura
Copyright © N. J. Chong and Z. Aziz. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
We aimed to assess the ecacy of Centella asiatica for improvement of the signs and symptoms of chronic venous insuciency
(CVI). We searched electronic databases including the Cochrane Central Register of Controlled Trials for randomised controlled
trials assessing the ecacy of Centella asiatica for CVI. Two review authors independently selected studies, assessed the risks of bias
of included studies and extracted data. e treatment eects of similar studies were pooled whenever appropriate. Eight studies met
the inclusion criteria. e pooling of data of similar studies showed that Centella asiatica signicantly improved microcirculatory
parameters such as transcutaneous partial pressure of CO2and O2, rate of ankle swelling and venoarteriolar response. ree out
of the eight studies did not provide quantitative data. However, these studies reported that patients treated with Centella asiatica
showed signicant improvement in CVI signs such as leg heaviness,p ainand o edema. Our results show that Centellaasiatica may be
benecial for improving signs and symptoms of CVI but this conclusion needs to be interpreted with caution as most of the studies
were characterised by inadequate reporting and thus had unclear risks of bias, which may threaten the validity of the conclusions.
1. Background
e term chronic venous insuciency (CVI) describes a
condition that aects the venous systems of the lower limbs.
It results from the obstruction or reux of blood ow in the
veins due to abnormalities of the venous wall and valves [].
Because of the abnormalities, venous blood ow is bidirec-
tional, resulting in inecient venous outow and high venous
pressure []. Symptoms of CVI may include leg discomfort,
heaviness, cramps, pains, oedema, and skin changes. e
most serious consequence of CVI is venous ulcers. CVI
causes considerable cost to society in terms of diagnosis,
treatments, loss of working hours, and impairment of quality
of life [,].
CVI is one of the most common diseases in the world [].
However, the exact prevalence in any population is dicult to
determine due to the limited availability of population-based
epidemiological studies. Some studies examined specic
groups or samples of hospital patients [,], while others
focus only on specic conditions such as varicose veins
or leg ulcers. Additionally ill-dened classications of CVI
make prevalence data dicult to interpret. Nevertheless, the
prevalenceofCVIisbelievedtobehighinwesternand
industrialised countries [,].
e aetiology of CVI is unclear, although it has been
knownthatitoccurswhenvenousbloodtransportisdis-
turbed in supercial or deep venous systems, the perforating
veins, or both []. Changes in the hemodynamics of the large
veins of the lower limbs are transmitted into the capillary
bed (microcirculation) and eventua lly results in chronic dam-
age and microcirculatory dysfunction []. is dysfunction,
also termed as venous microangiopathy, is associated with
increased capillary permeability which leads to the accumu-
lation of uid and becomes evident as oedema. e concept
Evidence-Based Complementary and Alternative Medicine
of venous microangiopathy permits the quantication of
microcirculatory parameters in CVI [].
Recently, several indirect tests have become available
which can provide quantitative assessment of the microcir-
culatory changes associated with CVI [,]. Changes in skin
ux and other microcirculatory parameters such as tran-
scutaneous partial pressure of oxygen (tcPO2), carbon diox-
ide (tcPCO2), capillary ltration rate (measured as rate of
ankle swelling), and venoarteriolar response (VAR) are use-
ful measures in the evaluation of venous microangiopathy
[]. For example, the tcPO2is decreased while tcPCO2is
increased in subjects with venous microangiopathy [].
Existing interventions that have been proven, or are likely,
to be therapeutically benecial in the treatment of CVI
include limb elevation, surgery and mechanical compression
[–]. Use of compression stockings is common for the
management of venous insuciency. However, poor compli-
ance is a well-known problem with compression stockings.
Additionally some patients are unable to use compression
stockings due to the condition of their limbs or their general
health [].
ere has been considerable interest in the role of phar-
macological agents to treat CVI. A number of drugs have
been used as adjunctive therapies in treatment of CVI includ-
ing aminaone and calcium dobesilate [,]. However,
there is not enough evidence to support the ecacy of these
agents for CVI [–].
Plant constituents which have been evaluated for the
treatment of signs and symptoms of CVI and venous micro-
angiopathy include diosmin, avonoids, and saponosides
[–]. Even though these plant constituents have been
shownintheshorttermtobeeectiveatreducingpainand
oedema related to symptoms of CVI, their long-term ecacy
has not been established [,]. One herb that has received
substantial attention for improving signs and symptoms of
CVI and microangiopathy of the lower limbs is Centella
asiatica [,]. e leaves of Centella asiatica contain triter-
penes which have been shown in animal studies to have anti-
inammatory properties [,] and promote wound healing
by stimulating collagen and glycosaminoglycan synthesis as
well as angiogenesis [,].
Several non systematic reviews have reviewed various
aspects of Centella asiatica including the chemistry, pharma-
cology, and clinical uses [,,–]. However, none of
thesereviewsfocusedontheevidencefortheuseofCentella
asiatica in CVI. For this reason, it was necessary to do an
objective and rigorous assessment of the evidence for the
ecacy of Centella asiatica for CVI.
2. Methods
2.1. Selection of Studies. We only considered randomised con-
trolled trials (RCTs) examining or describing the eectiveness
of Centella asiatica for improving signs and symptoms of
CVI and microangiopathy compared with placebo, standard
therapy or other active agents. Even though most of the
RCTs do not use specic diagnostic classication of CVI, we
included studies which recruited patients with CVI or venous
hypertension. We excluded studies assessing Centella asiatica
in combination with other active agents as well as studies
which recruited subjects with postthrombotic syndrome or
passengers on long ights.
2.2. Identication of Studies. We carried out a comprehensive
literature search for RCTs published from to June
withnorestrictiononthesourceandlanguageofthepublica-
tions. e search included electronic databases and cross-
referencing of articles. Among the databases searched were
OVID, Cochrane Library, MEDLINE, PubMed, MEDICAL
Databases @EBSCOhost, and Scopus. We also did hand
searches on publications published in English.
2.3. Data Collection and Risk of Bias Assessment. Two r e view
authors independently assessed the eligibility of studies from
the searches. Full reports of potentially eligible studies were
obtained for data extraction and assessment of their risk
of bias. Data were extracted using a prespecied extraction
form.
We extracted outcome data that reported any of the clin-
ical signs and symptoms of CVI such as leg oedema, skin
changes, leg discomfort (tingling, burning, itching, sensa-
tions of throbbing, or heaviness), and pain. Outcome data
which assessed microcirculatory parameters of microangio-
pathy such as rate of ankle swelling (RAS), tcPO2, tcPCO2,
and VAR were also extracted. We also extracted data on
adverse eects.
We assessed the risk of bias in the included studies based
on criteria published in the Cochrane Handbook for System-
atic Reviews of Interventions []. Any disagreements at the
stages from selecting studies to data extraction and risk of
bias assessment were resolved through discussions between
the two review authors.
2.4. Data Synthesis. e studies included in the review were
combined by narrative overview with a quantitative summary
of the results of similar trials if appropriate. Data pooling
of continuous data was performed using the weighted mean
dierence.
3. Results
3.1. Results of the Search. e search of electronic databases
and various sources identied potentially relevant articles
on Centella asiatica for CVI and microangiopathy (Figure ).
We screened the titles and abstracts for relevance and
excluded studies. Out of the full articles retrieved for
further evaluation, we excluded another eight studies. e
studies were excluded because they involved diabetic patients
[,], patients with postthrombotic syndrome [], ight
passengers [], nonrandomised controlled trial [], and
review papers [,,].
3.2. Description of the Studies. A total of eight studies met
the inclusion criteria: three recruiting patients with venous
insuciency of the lower limbs [–]andveinvolving
patients with venous hypertensions of the lower limbs [–]
(Table ).esamplesizesrangedfromtowithmean
sample size of and median . e duration of the trials
Evidence-Based Complementary and Alternative Medicine
225 records screened 209 records excluded
16 full-text articles assessed for eligibility 8 full-text articles
excluded with reasons
8 studies included in qualitative synthesis
5 studies included in quantitative synthesis
863 records aer removing duplicates
949 records identied
through database
searching
Included Eligibility Screening Identication
638 records excluded
37 additional records
identied through other
sources
F : Flow chart of result of searches, studies identied and included in this paper.
T : Characteristics of RCT on CVI and microangiopathy included in this study.
Study Participants Intervention (dose) 𝑛Duration of
study Control
Allegra et al., []Patients with venous
insuciency of the lower limbs TTFC A ( mg/day) days placeb o
Marastoni et al., []PatientswithCVI Centella asiatica extract
(tid)∗ weeks tribenoside
Pointel et al., []Patients with venous
insuciency of the lower limbs TTFCA ( mg; mg) weeks placebo
Cesarone et al., []Patients with chronic venous
hypertensive microangiopathy
TTFCA ( mg bid;
mg bid) days placebo
Cesarone et al., []
Patients with severe venous
hypertension, ankle swelling, and
lipodermatosclerosis
TTFCA ( mg bid) weeks placebo
Cesarone et al., []
Patients with venous
hypertension with ankle and foot
swelling, oedema, and
lipodermatosclerosis, with intact
skin
TTFCA ( mg bid) weeks placebo
De Sanctis et al., []
Patients with venous
hypertension (ambulatory
venous pressure > mm Hg)
TTFCA ( mg tid;
mg tid) weeks placebo
Incandela et al., []Patients with venous
hypertensive microangiopathy
TTFCA ( mg daily;
mg daily) weeks placebo
TTFCA: total triterpenic fraction of Centella asiatica.
∗Extract dosage not reported.
ranged from to days. Four studies were conducted in
Europe: Italy [,], France [], and UK [], while three
other studies [–] published by authors from Italy and UK
did not provide the setting of their studies.
3.3. Risk of Bias in Included Studies. e risk of bias in
the included studies is summarised in Figure .Adequate
sequence generation was reported in two trials [,]; the
other six trials have an unclear risk of bias from sequence
generation. In these six trials, there was no description of
how randomisation was achieved even though the authors
described the studies as RCT. e lack of description of the
allocation process also meant that the allocation concealment
was unclear.
In judging the risk of bias from blinding, we considered
who was blinded in the trial. We considered four trials
[,,,] to have a low risk of bias from blinding of
participants as participants in both treatment and control
groups received similar looking tablets. We were unable to
judgetheriskofbiasduetoblindinginfourothertrials
Evidence-Based Complementary and Alternative Medicine
Adequate sequence generation
Allocation concealment
Blinding (participant)
Blinding (care provider)
Blinding (outcome assessor)
Incomplete outcome data addressed (ITT)
Free of selective outcome reporting
Financial support
Group similar at baseline
Allegra et al., 1981 [38]
Marastoni et al., 1982 [39]
Pointel et al., 1987 [40]
Cesarone et al., 1994 [41]
Cesarone et al., 2001a [42]
Cesarone et al., 2001b [43]
De Sanctis et al., 2001 [44]
Incandela et al., 2001 [45]
+++
++
+
+
+
+?
+
+++
++
????
? ? ? ? ?
?
?
?
?
?
+? ??
? ? ? ????
????
? ? ? ? ?
?? ? ? ? ?? ?
? ? ????
?
?
?
+
+
+
+
+
Note: ITT: “intention-to-treat” analysis; indicates low risk of bias; indicates unclear risk of bias
+ ?
F : Risk of bias summary.
[,,,] as these trials did not provide information on
whether the participants, care provider, and outcome assessor
were blinded.
In judging the risk of bias from incomplete outcome
reporting, we considered whether missing data were imputed
appropriately and whether an intention-to-treat analysis was
reported for the outcomes. Only three trials [,,]were
considered to have low risk of bias from incomplete outcome
data.esetrialshavenolosstofollowup(dropout).Allthe
participants in these trials were reported to demonstrate very
good compliance and tolerance of Centella asiatica treatment
as no participants le the study before its completion. ere
was no information on the numbers lost to followup in one
trial []. Dropouts were reported in four other studies [–
,]. In two, these were due to side eects experienced with
Centella asiatica [,].
Selective outcome reporting has been dened as the selec-
tive reporting in a publication of only a selection of outcomes,
perhaps those based on statistically signicant results [].
In considering the risk of bias from the selective reporting,
we based our assessment on comparing outcomes listed
in the methods section of the paper with those outcomes
reported in the results section. None of the trials reported
the availability of the study protocol. Overall, the method
sections of the trials included did not explicitly state the
primary and secondary outcomes. One study []didnot
report all the outcomes which were mentioned in the method
section while two studies [,] reported several outcomes
which were not mentioned in the method section. us, we
considered these three studies to have unclear risk of bias
for selective reporting. We judged the risk of bias from the
selective reporting in the other ve trials [,–]tobe
low.
Wefocusedontwootherimportantaspectsofother
potential sources of bias that could threaten the validity of the
study’s ndings. e two risks were baseline comparability
andnancialsupportreceivedbythetrial.Fivetrials[–]
wereconsideredtobeatlowriskofbiasfrombaselinecom-
parability as there was no signicant dierence in baseline
between the treatment and control groups, while the risk of
this bias was not clear for the other three studies. None of the
eight studies provided information on the nancial support
for the study, and therefore we were unable to judge the risk
of bias due to sponsorship.
3.4. Eects of the Intervention. Even though most of the
included trials reported the eectiveness of Centella asiatica
in improving the signs and symptoms of CVI and microan-
giopathy compared to control, the ndings were dicult
to interpret as various outcome measures were used to
assess eectiveness. Several trials used subjective assessment
measures such as oedema, varicose veins, and leg heaviness
while other trials used objective measure of microcirculatory
Evidence-Based Complementary and Alternative Medicine
T : Outcomes assessed.
Study Outcome measures Conclusion
Allegra et al., []
Pain, heaviness, leg oedema,
trophic lesions, easy tiredness,
skin hypothermia, varicosities,
and tolerance
Improves venous reux in
patients
Marastoni et al., []
Night cramps, painful limbs,
numbness, heaviness, orthostatic
oedema, and altered skin
trophism
Improves clinical observations of
venous insuciency and venous
tone
Pointel et al., []
Venous distensibil it y, % o f
patients with improved heaviness
in legs, oedema, and standing leg
pain
TTFCA is well tolerated and
superior to placebo in the
treatment of venous insuciency
Cesarone et al., []RF,tcPCO
,andtcPO
Eective in venous hypertensive
microangiopathy
Cesarone et al., a [] RF, CFR (measured as RAS)
Improves microcirculation with
venous hypertension and venous
microangiopathy
Cesarone et al., b []RF,VAR,tcPCO
,tcPO
,andRT
Improves microcirculation and
leg volume in venous
hypertension
De Sanctis et al., [] CFR, RT
Reduces the increased capillary
ltration in patients with venous
hypertension
Incandela et al., [] BRF, VAR, tcPCO,andtcPO
Useful for treatment of venous
hypertensive microangiopathy
BRF: baseline resting ow.
CFR: capillary ltration rate.
tcPCO: transcutaneous pressure of carbon dioxide.
tcPO: transcutaneous pressure of oxygen.
RAS: rate of ankle swelling.
RF: resting ux.
RT: relling time.
VAR: venoarteriolar response.
parameters such as tcPCO2, tcPO2,andRAS(Ta b l e ). We
categorisedtheresultsintothefollowing.
3.4.1. Signs and Symptoms of CVI. ree trials [,,]
assessed treatment outcomes such as leg heaviness, oedema,
and pain but did not provide quantiable data. ese trials
reported qualitatively that the Centella asiatica group showed
signicantly greater improvement compared to the control
group in treating the signs and symptoms of CVI.
3.4.2. Microcirculatory Parameters. Two trials [,]pro-
vided data for rate of ankle swelling, but they were not
suciently homogenous for the data to be pooled. erefore,
we presented the data separately for each trial. Figures (a)
and (b) show there was a statistically signicant eect on
ankleswellinginfavourofTTFCAgroupaereightweeksof
treatment (MD −.; % CI −. to −.) and four weeks
of treatment (MD −.; % CI −. to −.), respectively.
e tcPO2and tcPCO2values were reported in three trials
[,,]involvingsubjects.etrialsweresuciently
homogenous to allow us to pool the results. Figure (c) shows
that the increase in tcPO2was signicantly higher in the
TTFCA group compared to the control group (WMD .;
%CI.to.)whileFigure (d) shows the decrease in
tcPCO2was signicantly greater favouring the TTFCA group
(WMD −. ; % C I −. to −.).
Only two studies [,]evaluatedVARusinglaser
doppler owmetry. One trial []involvingsubjects
provided quantiable data on VAR. Figure (e) shows there
was a statistically signicant eect on VAR in favour of
TTFCA group (MD ; % CI . to .).
3.5. Adverse Eects. Two trials reported on the adverse
eects [,]. Two patients given Centella asiatica extract
experienced minor stomach pain while one patient had to
stop treatment due to severe nausea []. Four patients given
TTFCA withdrew from the trial []: three due to nausea and
gastric pain and one because of “neurological absence.”
4. Discussion
isistherstpaperthatusesasystematicreviewmethod-
ology to evaluate the ecacy of Centella asiatica for the
management of the signs and symptoms of CVI. Except for
Evidence-Based Complementary and Alternative Medicine
−2−1012
Favours TTFCA Favours placebo
Study
Total (95% CI)
Heterogeneity: not applicable
mean (SD) 𝑁𝑁
22
22
mean (SD)
0.11 (0.16) 18
18
Weight
100.0%
100.0%
IV, xed, 95% CI
TTFCA Placebo Mean dierence Mean dierence
IV, xed, 95% CI
−
−
0.84 [−
−
0.94, −
−
0.74]
0.84 [ 0.94, 0.74]
Cesarone et al., 2001 [42] − 0.73 (0.17)
Test for overall eect: 𝑍= 16.06 (𝑃< 0.00001)
(a)
−2−1012
Favours TTFCA Favours placebo
Study
Total (95% CI)
Heterogeneity: not applicable
mean (SD)
20
20
mean (SD)
20
20
100.0%
100.0%
IV, xed, 95% CI
TTFCA Placebo Mean dierence Mean dierence
IV, xed, 95% CI
Weight
Test for overall eect: 𝑍=121.75(𝑃< 0.00001)
−0.78 (0.02) −0.01 (0.02) −0.77 [−0.78, −0.76]
De Sanctis et al., 2001 [44]
−0.77 [−0.78, −0.76]
𝑁𝑁
(b)
−20 −10 0 10 20
Favours placebo Favours TTFCA
Study
Total (95% CI)
mean (SD)
8 (6.59)
4 (12.73)
7 (6.01)
31
20
33
84
mean (SD)
0.9 (7.08)
1 (10.63)
0 (7.30)
27
20
27
74
Weight
43.5%
10.3%
46.2%
100.0%
IV, xed, 95% CI
7.10 [3.56, 10.64]
7.00 [3.57, 10.43]
6.63 [4.30, 8.96]
TTFCA Placebo Weighted mean dierence Weighted mean dierence
IV, xed, 95% CI
Cesarone et al., 1994 [41]
Cesarone et al., 2001 [43]
Incandela et al., 2001 [45]
Test for overall eect: 𝑍=5.57(𝑃< 0.00001)
3.00 [− 4.27, 10.27]
𝑁𝑁
Heterogeneity: 𝜒2= 1.07,df=2(𝑃 = 0.59); 𝐼2=0%
(c)
−20 −10 0 10 20
Favours placeboFavours TTFCA
Study
Total (95% CI)
mean (SD)
31
20
33
84
mean (SD)
1 (9.22)
27
20
27
74
43.5%
12.5%
44.0%
100.0%
IV, xed, 95% CI
TTFCA Placebo Weighted mean dierence
IV, xed, 95% CI
Weight Weighted mean dierence
Test for overall eect: 𝑍=7.26 (𝑃< 0.00001)
Cesarone et al., 1994 [41]
Cesarone et al., 2001 [43]
Incandela et al., 2001 [45]
−8.00 [−11.07, −4.93]
−4.00 [−9.71, 1.71]
−8.00 [−11.05, −4.95]
− 7.50 [−9.52, −5.47]
−9 (5.04)
−3 (9.22)
−9 (4.98)
−1 (6.64)
−1 (6.72)
𝑁𝑁
Heterogeneity: 𝜒2= 1.65,df=2(𝑃 = 0.44); 𝐼2=0%
(d)
−100 −50 0 50 100
Favours placebo Favours TTFCA
Study
Total (95% CI)
Heterogeneity: not applicable
mean (SD)
75 (27.1) 33
33
mean (SD)
1 (27.9) 27
27
Weight
100.0%
100.0%
IV, xed, 95% CI
74.00 [59.99, 88.01]
74.00 [59.99, 88.01]
TTFCA Mean dierence
IV, xed, 95% CI
Placebo
Incandela et al., 2001 [45]
Test for overall eect: 𝑍= 10.35 (𝑃< 0.00001)
Mean dierence
𝑁𝑁
(e)
F : (a) Comparison: total triterpenoid fraction of Centella asiatica (TTFCA) versus placebo for eight weeks; outcome: rate of ankle
swelling (mL/min per mL). (b) Comparison: TTFCA versus placebo for four weeks; outcome: rate of ankle swelling (mL/ mL per
min). (c) Comparison: TTFCA versus placebo; outcome: transcutaneous partial pressure of oxygen (mmHg). (d) Comparison: TTFCA
versus placebo; outcome: transcutaneous partial pressure of carbon dioxide (mmHg). (e) Comparison: TTFCA versus placebo; outcome:
venoarteriolar response (mV).
Evidence-Based Complementary and Alternative Medicine
thehandsearches,therewasarestrictiononthelanguageof
publications. We contacted several authors and researchers
directly for further data on the outcome of interest, but very
few of them responded. e absence of adequate data from
eligible studies for the outcome of interest is a common
problem encountered in most meta-analysis [–]. We did
not attempt to use several available statistical procedures for
handling missing outcome data because all have weaknesses
[]. Pooling the results of the individual studies would give
larger sample size and therefore increase the statistical power
to determine treatment eects [,]. However, we were
unable to pool the results of several studies because outcome
data were missing.
Measuring the outcomes of interventions in CVI is
dicult. ere is no single test which can serve as a common
index of change following the intervention. Measuring ambu-
latory venous pressure (AVP) which is equivalent to the ankle
arterial pressure is invasive. Several noninvasive physiological
tests which are based on microcirculatory parameters are not
suitable as surrogates for AVP. Besides, current physiological
tests are not standardised and do not provide established nor-
malvaluestogiveanobjectivemeasureofeectsfollowing
treatment.
e outcomes of the treatment of CVI with Centella
asiatica in the trials we have reviewed should be interpreted
with caution as only one trial [] had a low risk of bias from
the blinding of both of the participant and outcome assessor.
Forsubjectivemeasuressuchaspain,theblindingofoutcome
assessor is crucial [].
Improvements in microcirculatory parameters are usu-
ally associated with improved signs and symptoms of CVI
[,]. It is possible that decreased tcPCO2reduces vaso-
dilatation and capillary permeability thus resulting in impro-
vement in oedema []. e results seem to suggest that
TTFCA improves RAS, VAR, tcPO2, and tcPCO2.However,
these ndings should be interpreted with caution since
normal values for these parameters are not well established.
Values that constitute statistically signicant dierences from
pretreatment values between treatment and control group
may not be clinically signicant. e result of this study is
in agreement with other nonsystematic reviews [,]in
that evidence for the ecacy of Centella asiatica extract for
CVIisinconclusive.isisprobablyduetothecomplexityof
measuring outcomes in CVI.
4.1. Limitations. ere were several limitations to our paper.
First, designing a search strategy to locate all trials on
Centella asiatica for CVI and microangiopathy is not easy. We
recognised that we might have missed out studies published
in non-English publications. However, a more comprehensive
hand search for non-English articles would be costly and
time consuming. erefore, these missing studies may have
limited the completeness of our paper.
Second, none of the included studies used the currently
accepted CEAP classication for the diagnosis of CVI. Five
studiesusedspecieddiagnosticcriteriaforCVI[–].
However, not all these studies used the same criteria. ree
studies [–] did not disclose the criteria used to diagnose
CVI or microangiopathy. erefore, the characteristics of the
subjects included in these studies in terms of degree of pro-
gression of CVI and microangiopathy may be heterogeneous
amongthestudies.iscouldpotentiallyleadtodierences
in response to treatment across the dierent studies.
ird, the studies used dierent measures to assess the
signs and symptoms of CVI as well as dierent physiological
tests to evaluate circulatory parameters following treatment.
Subjectiveoutcomemeasuressuchaspain,oedema,and
heaviness made the interpretation of the results in three trials
dicult. ese trials may be at risk of bias particularly as they
did not adequately report on the methods used to blind the
outcome assessors. Lack of blinding in RCTs has been shown
to be associated with more exaggerated estimates of treatment
eects [].
Fourth,itwasdiculttoassesstheriskofbiasformost
of the included studies. We were unable to verify the required
information from the authors as they did not response to
most of our requests for additional information. erefore,
theriskofbiasinmostoftheincludedstudiesissomewhat
unclear. Sequence generation, allocation concealment, and
blinding are not adequately reported. It is dicult to know
whether this is due to poor design or conduct of the trial.
However, trials that omit important methodological details
have been associated with biased overestimates of treatment
eects [].
Despite these limitations, we have not restricted our paper
to trials with specied methodological characteristics or trials
that report on a particular outcome. e use of narrow
inclusion criteria would have dealt with the heterogeneity
challenges, but we would risk losing information on how
trials on Centella asiatica are conducted and thus would not
be able to highlight the shortcomings of the available trials for
the benet of future trials.
5. Conclusion
e eight trials of Centella asiatica we included in this
paper all reported benecial eects of plant extract on CVI.
However, the extent to which we can draw conclusions
about the benecial eects of Centella asiatica on CVI and
microangiopathy is still limited. ere are some suggestions
of ecacy on some physiological parameters although the
clinical relevance of these results is uncertain due to an
absence of well-established normal values for the circulatory
parameters. e positive eects on the circulator y parameters
of microangiopathy should also be interpreted with caution,
giventhattherisksofbiasinmostofthestudiesareunclear.
Due to the limitations of current evidence, the need for
better quality RCTs to evaluate the ecacy of Centella asiatica
is warranted. Future trials should dene accurately CVI and
microangiopathy using CEAP classications, and the RCTS
should be adequately reported using the CONSORT
Statement [].
Acknowledgments
e authors are indebted to the authors who have responded
to their request for full-text journal articles or provided
further information on the study. is work was supported
Evidence-Based Complementary and Alternative Medicine
by Postgraduate Research Fund (PS/C) of Institute
of Research Management and Monitoring, University of
Malaya.
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